Influence of body weight on bone mass, architecture and turnover

Abstract

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating the development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. Although the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size.

Keywords: fracture risk; leptin; mechanical strain; osteoporosis; weight change.

Figure 1

The mechanostat is hypothesized as a mechanism that regulates bone mass in response to changes in mechanical strain. As originally envisioned (A), strain levels consistently falling below the lower boundary lead to an adaptive response where bone is lost, increasing strain. Strain levels consistently exceeding the upper boundary lead to an adaptive response where bone is gained, decreasing strain. Based on this model there is a zone between upper and lower boundaries where strain differences do not evoke an adaptive response (Frost 1987). An alternative model has been proposed (B) where strain levels below or above a set point that is bone specific evokes an adaptive response (Skerry 2006). While some studies suggest that moderate weight changes need not evoke an adaptive response (see text) other findings are consistent with the alternative model (see Figure 2).

Figure 2

Leptin alters the sensitivity of the skeleton to body weight changes. Total femur mass is strongly associated with body weight in 7-week-old female WT, partially leptin deficient ob/+, and leptin-deficient ob/ob mice fed a normal diet. ob/+ have near normal leptin levels due to increased fat mass and demonstrate an association between body weight and bone mass nearly identical to WT mice. In contrast, ob/ob mice require a much higher body weight to achieve a bone mass equivalent to WT. Please note that the slope of the regression lines is less than unity (0.49 for WT and ob/+ mice and 0.34 for ob/ob mice); increasing body weight by 50% in a WT mouse would be expected to lead to ~25% increase in bone mass. Reproduced, with permission, from Philbrick KA, Turner RT, Branscum AJ, Wong CP & Iwaniec UT (2015) Paradoxical effects of partial leptin deficiency on bone in growing female mice, The Anatomical Record 298 2018–2029. Copyright 2015 Wiley Periodicals, Inc.

Figure 3

The complex relationship between BMI, BMD and fracture risk is illustrated in the schematic. Compared to an underweight individual, an overweight individual experiencing a fall from the same height would generate a proportionately greater load on a limb (ground reaction force). However, the presence of greater amount of soft tissue in the heavier individual should attenuate more of the load and distribute the remaining load over a larger bone surface, reducing peak strain such that the effective load could be greater in the lighter individual. Assuming equivalent bone quality, the higher BMD typical in the heavier individual would be a further advantage in reducing strain below that required for a fracture. However, based on epidemiological studies, further increases in weight may provide a diminishing return because the reductions in load during a fall related to soft tissue and higher BMD may not fully compensate for increased weight.